A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength

Signaling via the T cell receptor (TCR) is critical during the development, maintenance, and activation of T cells. Quantitative aspects of TCR signaling have an important role during positive and negative selection, lineage choice, and ability to respond to small amounts of antigen. By using a muta...

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Detalles Bibliográficos
Autores: Bovolenta, Elena R., García-Cuesta, Eva M, Horndler, Lydia, Ponomarenko, Julia, Schamel, Wolfgang W, Mellado, Mario, Castro, Mario, Abia, David, Santen, Hisse M. van
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/349975
Acceso en línea:http://hdl.handle.net/10261/349975
https://api.elsevier.com/content/abstract/scopus_id/85130966020
Access Level:acceso abierto
Palabra clave:diversity
pre-TCR
repertoire
signaling
β-selection
Descripción
Sumario:Signaling via the T cell receptor (TCR) is critical during the development, maintenance, and activation of T cells. Quantitative aspects of TCR signaling have an important role during positive and negative selection, lineage choice, and ability to respond to small amounts of antigen. By using a mutant mouse line expressing a hypomorphic allele of the CD3ζ chain, we show here that the strength of pre-TCR–mediated signaling during T cell development determines the diversity of the TCRβ repertoire available for positive and negative selection, and hence of the final αβTCR repertoire. This finding uncovers an unexpected, pre-TCR signaling–dependent and repertoire–shaping role for β-selection beyond selection of in-frame rearranged TCRβ chains. Our data furthermore support a model of pre-TCR signaling in which the arrangement of this receptor in stable nanoclusters determines its quantitative signaling capacity.